Evolution of Bacterial Copper Resistance

这个项目是为了研究与植物相关的细菌如何适应环境中有毒的铜水平。铜是一种重要的杀菌剂，常用于农业植物病害防治。植物病原菌中铜抗性的发展可能对铜在植物疾病控制中的未来应用构成威胁，更好地了解这种抗性如何发展对评估这种威胁至关重要。对铜抗性的认识已经导致了开发新的铜配方的尝试，这些配方可以绕过抗性机制，而对抗性的生理和调节机制的更深入了解可以加强这一努力。微生物对非必需有毒金属（如汞）的耐药性已经进行了广泛的研究，但对铜的耐药性却很少受到关注。不像其他金属。爱的生物体需要铜作为某些酶的组成部分；在低水平是有益的，但在高水平是有毒的。因此，微生物种群中铜抗性的进化涉及到铜吸收和排铜机制的复杂平衡。对铜抗性决定基因进行了克隆和鉴定，发现它们与铜敏感菌的一组染色体基因有关。我们已经证明，抗性可以通过这些染色体基因的修饰而进化，目前的项目是进一步定义这些修饰。由于微生物需要铜作为微量元素，因此必须严格控制阻止铜吸收的抗性机制，以便在正常生长条件下不排除铜。我们有证据表明，在这个系统中基因表达水平的改变。细菌产生的其他蛋白质的铜结合能力在铜排斥机制中很重要，我们将研究这些蛋白质的铜结合位点在耐药性进化过程中是如何被修饰的。

9306559 Cooksey This project is to investigate how plant associated bacteria adapt to toxic levels of copper in the environment. Copper is an important bactericide used frequently for disease control on agricultural plants. The development of copper resistance in plant pathogenic bacteria may pose a threat to the future use of copper in plant disease control, and a better understanding of how this resistance develops will be important for evaluating this threat. The recognition of copper resistance has already led to attempts to develop new copper formulations that may circumvent resistance mechanisms, and a greater understanding of the physiological and regulatory mechanisms of resistance could enhance that effort. %%% Microbial resistance to nonessential toxic metals, such as mercury, has been studied extensively, but resistance to copper has receives much less attention. Unlike the other metals. copper is required by loving organisms as a component of certain enzymes; at low levels it is beneficial, but at high levels it is toxic. The evolution of copper resistance in microbial populations therefore involves a complex balance in copper uptake and exclusion mechanisms. The genes determining copper resistance were cloned and characterized, and they were found to be related to a set of chromosomal genes found in copper sensitive bacteria. We have shown that the resistance can evolve through modifications of these chromosomal genes, and the present project is to define further these modifications. Since copper is required by microorganisms as a trace element, the resistance mechanism, which prevents uptake of copper, must be under tight regulatory control so that copper is not excluded under normal growth conditions. We have evidence that modifications in the level in gene expression in this system. The copper binding capacity of other proteins produced by the bacterium is important in the copper exclusion mechanism, and we will study how copper binding sites of these proteins have been modified during the evolution of resistance.